Formaldehyde → HCID 58438351, compound

HRID 2168720Notes

Reaction equation

HRID 2168720 reaction equation
Cl.Cl.[CH:3]1([C:7]2[N:8]=[N:9][C:10]([O:26][CH:27]3[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]3)=[CH:11][C:12]=2[C:13]2[CH:18]=[CH:17][C:16]([O:19][CH:20]3[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]3)=[CH:15][CH:14]=2)[CH2:6][CH2:5][CH2:4]1.[CH2:33]=O.[C:35](O[BH-](OC(=O)C)OC(=O)C)(=O)[CH3:36]>C(Cl)Cl>[CH:3]1([C:7]2[N:8]=[N:9][C:10]([O:26][CH:27]3[CH2:28][CH2:29][N:30]([CH3:33])[CH2:31][CH2:32]3)=[CH:11][C:12]=2[C:13]2[CH:14]=[CH:15][C:16]([O:19][CH:20]3[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]3)=[CH:17][CH:18]=2)[CH2:6][CH2:36][CH2:35][CH2:5][CH2:4]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 2724942TriacetoxyborohydrideHCID 67372091HCID 67372091, compound

Product 1

HCID 58438351HCID 58438351, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-cyclobutyl-4-(4-cyclohexyloxy-phenyl)-6-(piperidin-4-yloxy)-pyridazine dihydrochloride (0.17 mmol, 0.08 g) and aqueous formaldehyde (37%, 0.83 mmol, 0.07 mL) in dry DCM (1 mL) was added macroporous resin-bound triacetoxyborohydride (loading 2.36 mmol/gram, 1.0 mmol, 0.42 g). The mixture was shaken for 12 hours. The reaction was placed directly onto a 4 g SiO2 cartridge and the column was eluted with 0-6% (2N NH3 in MeOH) in DCM to give 3-cyclohexyl-4-(4-cyclohexyloxy-phenyl)-6-(1-methyl-piperidin-4-yloxy)-pyridazine. The neutral amine was treated with 2N HCl in diethyl ether (1 mL) and DCM (1 mL). The volatiles were removed under reduced pressure and the salt was triturated with diethyl ether and filtered to provide the title compound (0.05 g). LCMS: m/z 423 [M+1]. 1H NMR (400 MHz, CD3OD) δ 7.26-7.47 (3 H, m), 7.02-7.11 (2 H, m), 5.35-5.60 (1 H, m), 4.37-4.48 (1 H, m), 3.97-4.13 (1 H, m), 3.67 (1 H, d), 3.23-3.53 (2 H, m), 2.92 (3 H, s), 1.95-2.62 (12 H, m), 1.75-1.92 (3 H, m), 1.29-1.68 (6 H, m).

Workup

  1. washthe column was eluted with 0-6% (2N NH3 in MeOH) in DCM

Sources & evidence

ORD record
ord-00902a6104dc4b10adfd418e82feb9c9
Source dataset
uspto-grants-2015_06
Patent number
US09045461B2

Reaction notes

Loading…